Hepatic impairment as a risk factor of adverse drug reactions
- Authors: Ostroumova O.D.1,2, Pereverzev A.P.1
-
Affiliations:
- Russian Medical Academy of Continuous Professional Education
- Sechenov First Moscow State Medical University (Sechenov University)
- Issue: Vol 23, No 12 (2021)
- Pages: 939-948
- Section: Articles
- URL: https://journals.rcsi.science/2075-1753/article/view/100022
- DOI: https://doi.org/10.26442/20751753.2021.12.201234
- ID: 100022
Cite item
Full Text
Abstract
There are a lot of clinical variants of hepatic impairment ranging from asymptomatic increase in transaminases to acute liver failure and fulminant hepatitis. Hepatic impairment is a polietiologic syndrome. According to the epidemiological study conducted in the United States (1998–2008), the main causes of hepatic impairment were paracetamol overdose (46%), idiopathic liver dysfunction (14%), other drugs (excluding paracetamol, 11%), viral hepatitis B (7%), other infectious and non-infectious diseases with liver damage (except for viral hepatitis) – 7%, autoimmune hepatitis (5%), ischemic hepatitis (syn. hypoxic hepatitis, liver infarction) – 4%, viral hepatitis A (3%) and Wilson's disease (2%). Hepatic impairment have a direct impact on the pharmacokinetics and pharmacodynamics of drugs decreasing clearance, elimination and excretion of drugs. Also Transjugular intrahepatic porto-systemic shunts, which are often used to treat portal hypertension in patients with liver cirrhosis, can significantly reduce the presystemic elimination of drugs, thereby increasing their absorption. Moreover, in patients with liver cirrhosis, concomitant renal dysfunction also requires an adjustment of the dose of drugs. Correction of pharmacotherapy in accordance to pharmacokinetic and pharmacodynamic changes of drugs ingested by patients with impaired liver function will improve the quality of medical care and reduce the risks of adverse drug reactions.
Full Text
##article.viewOnOriginalSite##About the authors
Olga D. Ostroumova
Russian Medical Academy of Continuous Professional Education; Sechenov First Moscow State Medical University (Sechenov University)
Email: ostroumova.olga@mail.ru
ORCID iD: 0000-0002-0795-8225
SPIN-code: 3910-6585
D. Sci. (Med.), Prof.
Russian Federation, Moscow; MoscowAnton P. Pereverzev
Russian Medical Academy of Continuous Professional Education
Author for correspondence.
Email: acchirurg@mail.ru
ORCID iD: 0000-0001-7168-3636
SPIN-code: 4842-3770
Cand. Sci. (Med.)
Russian Federation, MoscowReferences
- Lee WM, Squires RH Jr, Nyberg SL, et al. Acute liver failure: Summary of a workshop. Hepatology. 2008;47(4):1401-15. doi: 10.1002/hep.22177
- Ichai P, Faria L, Saliba F, et al. Improvement of survival in fulminant hepatitis in the recent years. Hepatology. 2006;44(Suppl. 4):371A.
- Brandsaeter B, Höckerstedt K, Friman S, et al. Fulminant hepatic failure: outcome after listing for highly urgent liver transplantation – 12 years experience in the nordic countries. Liver Transpl. 2002;8(11):1055-62. doi: 10.1053/jlts.2002.35556
- Ichai P, Samuel D. Epidemiology of liver failure. Clin Res Hepatol Gastroenterol. 2011;35(10):610-7. doi: 10.1016/j.clinre.2011.03.010
- Child CG, Turcotte JG. Surgery and portal hypertension. Major Probl Clin Surg. 1964;1:1-85.
- Pugh RN, Murray-Lyon IM, Dawson JL, et al. Transection of the oesophagus for bleeding oesophageal varices. Br J Surg. 1973;60(8):646-9. doi: 10.1002/bjs.1800600817
- Quigley EM. Gastrointestinal dysfunction in liver disease and portal hypertension. Gut-liver interactions revisited. Dig Dis Sci. 1996;41(3):557-61. doi: 10.1007/BF02282341
- Zuckerman MJ, Menzies IS, Ho H, et al. Assessment of intestinal permeability and absorption in cirrhotic patients with ascites using combined sugar probes. Dig Dis Sci. 2004;49(4):621-6. doi: 10.1023/b:ddas.0000026307.56909.21
- Verbeeck RK. Pharmacokinetics and dosage adjustment in patients with hepatic dysfunction. Eur J Clin Pharmacol. 2008;64(12):1147-61. doi: 10.1007/s00228-008-0553-z
- Blaschke TF, Rubin PC. Hepatic first-pass metabolism in liver disease. Clin Pharmacokinet. 1979;4(6):423-32. doi: 10.2165/00003088-197904060-00002
- Pentikäinen PJ, Neuvonen PJ, Jostell KG. Pharmacokinetics of chlormethiazole in healthy volunteers and patients with cirrhosis of the liver. Eur J Clin Pharmacol. 1980;17(4):275-84. doi: 10.1007/BF00625801
- Neugebauer G, Gabor M, Reiff K. Disposition of carvedilol enantiomers in patients with liver cirrhosis: evidence for disappearance of stereoselective first-pass extraction. J Cardiovasc Pharmacol. 1992;19(Suppl. 1):S142-6. doi: 10.1097/00005344-199219001-00028
- Chalasani N, Gorski JC, Patel NH, et al. Hepatic and intestinal cytochrome P450 3A activity in cirrhosis: effects of transjugular intrahepatic portosystemic shunts. Hepatology. 2001;34(6):1103-8. doi: 10.1053/jhep.2001.29306
- Gorski JC, Jones DR, Haehner-Daniels BD, et al. The contribution of intestinal and hepatic CYP3A to the interaction between midazolam and clarithromycin. Clin Pharmacol Ther. 1998;64(2):133-43. doi: 10.1016/S0009-9236(98)90146-1
- Wilcock A, Charlesworth S, Prentice W, et al. Prescribing in Chronic Severe Hepatic Impairment. J Pain Symptom Manage. 2019;58(3):515-37. doi: 10.1016/j.jpainsymman.2019.04.034
- MacKichan JJ. Influence of protein binding and use of unbound (free) drug concentrations. In: Applied pharmacokinetics & pharmacodynamics – principles of therapeutic drug monitoring. Ed. ME Burton, LM Shaw, JJ Schentag, WE Evans. Lippincott Williams & Wilkins, Philadelphia, 2006; p. 82-120.
- Blaschke TF. Protein binding and kinetics of drugs in liver diseases. Clin Pharmacokinet. 1977;2(1):32-44. doi: 10.2165/00003088-197702010-00003
- El Touny M, el Guinaidy M, Abdel Bary M, et al. Pharmacokinetics of cefodizime in patients with liver cirrhosis and ascites. Chemotherapy. 1992;38(4):201-5. doi: 10.1159/000239001
- Williams RL, Upton RA, Cello JP, et al. Naproxen disposition in patients with alcoholic cirrhosis. Eur J Clin Pharmacol. 1984;27(3):291-6. doi: 10.1007/BF00542162
- Morgan DJ, McLean AJ. Clinical pharmacokinetic and pharmacodynamic considerations in patients with liver disease. An update. Clin Pharmacokinet. 1995;29(5):370-91. doi: 10.2165/00003088-199529050-00005
- Reichen J. The Role of the Sinusoidal Endothelium in Liver Function. News Physiol Sci. 1999;14:117-21. doi: 10.1152/physiologyonline.1999.14.3.117
- Morgan DJ, McLean AJ. Therapeutic implications of impaired hepatic oxygen diffusion in chronic liver disease. Hepatology. 1991;14(6):1280-2.
- George J, Murray M, Byth K, Farrell GC. Differential alterations of cytochrome P450 proteins in livers from patients with severe chronic liver disease. Hepatology. 1995;21(1):120-8.
- George J, Liddle C, Murray M, et al. Pre-translational regulation of cytochrome P450 genes is responsible for disease-specific changes of individual P450 enzymes among patients with cirrhosis. Biochem Pharmacol. 1995;49(7):873-81. doi: 10.1016/0006-2952(94)00515-n
- Furlan V, Demirdjian S, Bourdon O, et al. Glucuronidation of drugs by hepatic microsomes derived from healthy and cirrhotic human livers. J Pharmacol Exp Ther. 1999;289(2):1169-75.
- Villeneuve JP, Pichette V. Cytochrome P450 and liver diseases. Curr Drug Metab. 2004;5(3):273-82. doi: 10.2174/1389200043335531
- Elbekai RH, Korashy HM, El-Kadi AO. The effect of liver cirrhosis on the regulation and expression of drug metabolizing enzymes. Curr Drug Metab. 2004;5(2):157-67. doi: 10.2174/1389200043489054
- Adedoyin A, Arns PA, Richards WO, et al. Selective effect of liver disease on the activities of specific metabolizing enzymes: investigation of cytochromes P450 2C19 and 2D6. Clin Pharmacol Ther. 1998;64(1):8-17. doi: 10.1016/S0009-9236(98)90017-0
- Branch RA. Drugs in liver disease. Clin Pharmacol Ther. 1998;64(4):462-5. doi: 10.1016/S0009-9236(98)90077-7
- Frye RF, Zgheib NK, Matzke GR, et al. Liver disease selectively modulates cytochrome P450-mediated metabolism. Clin Pharmacol Ther. 2006;80(3):235-45. doi: 10.1016/j.clpt.2006.05.006
- Wang H, Liao ZX, Chen M, Hu XL. Effects of hepatic fibrosis on ofloxacin pharmacokinetics in rats. Pharmacol Res. 2006;53(1):28-34. doi: 10.1016/j.phrs.2005.08.005
- Hoyumpa AM, Schenker S. Is glucuronidation truly preserved in patients with liver disease? Hepatology. 1991;13(4):786-95.
- Levy M, Caraco Y, Geisslinger G. Drug acetylation in liver disease. Clin Pharmacokinet. 1998;34(3):219-26. doi: 10.2165/00003088-199834030-00004
- Pentikäinen PJ, Välisalmi L, Himberg JJ, Crevoisier C. Pharmacokinetics of midazolam following intravenous and oral administration in patients with chronic liver disease and in healthy subjects. J Clin Pharmacol. 1989;29(3):272-7. doi: 10.1002/j.1552-4604.1989.tb03327.x
- Shull HJ, Wilkinson GR, Johnson R, Schenker S. Normal disposition of oxazepam in acute viral hepatitis and cirrhosis. Ann Intern Med. 1976;84(4):420-5. doi: 10.7326/0003-4819-84-4-420
- Kraus JW, Desmond PV, Marshall JP, et al. Effects of aging and liver disease on disposition of lorazepam. Clin Pharmacol Ther. 1978;24(4):411-9. doi: 10.1002/cpt1978244411
- Ghabrial H, Desmond PV, Watson KJ, et al. The effects of age and chronic liver disease on the elimination of temazepam. Eur J Clin Pharmacol. 1986;30(1):93-7. doi: 10.1007/BF00614203
- Klotz U, Antonin KH, Brügel H, Bieck PR. Disposition of diazepam and its major metabolite desmethyldiazepam in patients with liver disease. Clin Pharmacol Ther. 1977;21(4):430-6. doi: 10.1002/cpt1977214430
- Debinski HS, Lee CS, Danks JA, et al. Localization of uridine 5'-diphosphate-glucuronosyltransferase in human liver injury. Gastroenterology. 1995;108(5):1464-9. doi: 10.1016/0016-5085(95)90695-9
- Mazoit JX, Sandouk P, Scherrmann JM, Roche A. Extrahepatic metabolism of morphine occurs in humans. Clin Pharmacol Ther. 1990;48(6):613-8. doi: 10.1038/clpt.1990.203
- Macdonald JI, Wallace SM, Mahachai V, Verbeeck RK. Both phenolic and acyl glucuronidation pathways of diflunisal are impaired in liver cirrhosis. Eur J Clin Pharmacol. 1992;42(5):471-4. doi: 10.1007/BF00314852
- Hildebrand M, Hellstern A, Hümpel M, et al. Plasma levels and urinary excretion of lormetazepam in patients with liver cirrhosis and in healthy volunteers. Eur J Drug Metab Pharmacokinet. 1990;15(1):19-26. doi: 10.1007/BF03190123
- Sonne J, Andreasen PB, Loft S, et al. Glucuronidation of oxazepam is not spared in patients with hepatic encephalopathy. Hepatology. 1990;11(6):951-6. doi: 10.1002/hep.1840110607
- Marcellin P, de Bony F, Garret C, et al. Influence of cirrhosis on lamotrigine pharmacokinetics. Br J Clin Pharmacol. 2001;51(5):410-4. doi: 10.1046/j.1365-2125.2001.01389.x
- Taburet AM, Naveau S, Zorza G, et al. Pharmacokinetics of zidovudine in patients with liver cirrhosis. Clin Pharmacol Ther. 1990;47(6):731-9. doi: 10.1038/clpt.1990.101
- Parker G, Bullingham R, Kamm B, Hale M. Pharmacokinetics of oral mycophenolate mofetil in volunteer subjects with varying degrees of hepatic oxidative impairment. J Clin Pharmacol. 1996;36(4):332-44. doi: 10.1002/j.1552-4604.1996.tb04209.x
- Crotty B, Watson KJ, Desmond PV, et al. Hepatic extraction of morphine is impaired in cirrhosis. Eur J Clin Pharmacol. 1989;36(5):501-6. doi: 10.1007/BF00558076
- Congiu M, Mashford ML, Slavin JL, Desmond PV. UDP glucuronosyltransferase mRNA levels in human liver disease. Drug Metab Dispos. 2002;30(2):129-34. doi: 10.1124/dmd.30.2.129
- Klaassen CD, Watkins JB 3rd. Mechanisms of bile formation, hepatic uptake, and biliary excretion. Pharmacol Rev. 1984;36(1):1-67.
- Mortimer PR, Mackie DB, Haynes S. Ampicillin levels in human bile in the presence of biliary tract disease. Br Med J. 1969;3(5662):88-9. doi: 10.1136/bmj.3.5662.88
- Sales JE, Sutcliffe M, O'Grady F. Cephalexin levels in human bile in presence of biliary tract disease. Br Med J. 1972;3(5824):441-3. doi: 10.1136/bmj.3.5824.441
- Brown RB, Martyak SN, Barza M, et al. Penetration of clindamycin phosphate into the abnormal human biliary tract. Ann Intern Med. 1976;84(2):168-70. doi: 10.7326/0003-4819-84-2-168
- Leung JW, Chan RC, Cheung SW, et al. The effect of obstruction on the biliary excretion of cefoperazone and ceftazidime. J Antimicrob Chemother. 1990;25(3):399-406. doi: 10.1093/jac/25.3.399
- Van Delden OM, van Leeuwen DJ, Jansen PL, et al. Biliary excretion of ceftriaxone into non-stagnant and stagnant bile. J Antimicrob Chemother. 1994;33(1):193-4. doi: 10.1093/jac/33.1.193
- Van den Hazel SJ, de Vries XH, Speelman P, et al. Biliary excretion of ciprofloxacin and piperacillin in the obstructed biliary tract. Antimicrob Agents Chemother. 1996;40(11):2658-60. doi: 10.1128/AAC.40.11.2658
- González G, Arancibia A, Rivas MI, et al. Pharmacokinetics of furosemide in patients with hepatic cirrhosis. Eur J Clin Pharmacol. 1982;22(4):315-20. doi: 10.1007/BF00548399
- Marcantonio LA, Auld WH, Murdoch WR, et al. The pharmacokinetics and pharmacodynamics of the diuretic bumetanide in hepatic and renal disease. Br J Clin Pharmacol. 1983;15(2):245-52. doi: 10.1111/j.1365-2125.1983.tb01493.x
- Cello JP, Oie S. Cimetidine disposition in patients with Laennec's cirrhosis during multiple dosing therapy. Eur J Clin Pharmacol. 1983;25(2):223-9. doi: 10.1007/BF00543795
- Smith IL, Ziemniak JA, Bernhard H, et al. Ranitidine disposition and systemic availability in hepatic cirrhosis. Clin Pharmacol Ther. 1984;35(4):487-94. doi: 10.1038/clpt.1984.65
- Brockmöller J, Thomsen T, Wittstock M, et al. Pharmacokinetics of levetiracetam in patients with moderate to severe liver cirrhosis (Child-Pugh classes A, B, and C): characterization by dynamic liver function tests. Clin Pharmacol Ther. 2005;77(6):529-41. doi: 10.1016/j.clpt.2005.02.003
- Granneman GR, Mahr G, Locke C, et al. Pharmacokinetics of temafloxacin in patients with liver impairment. Clin Pharmacokinet. 1992;22(Suppl. 1):24-32. doi: 10.2165/00003088-199200221-00006
- Caujolle B, Ballet F, Poupon R. Relationship among beta-adrenergic blockade, propranolol concentration, and liver function in patients with cirrhosis. Scand J Gastroenterol. 1988;23(8):925-30. doi: 10.3109/00365528809090148
- Ramond MJ, Comoy E, Lebrec D. Alterations in isoprenaline sensitivity in patients with cirrhosis: evidence of abnormality of the sympathetic nervous activity. Br J Clin Pharmacol. 1986;21(2):191-6. doi: 10.1111/j.1365-2125.1986.tb05174.x
- Dao MT, Villeneuve JP. Kinetics and dynamics of triamterene at steady-state in patients with cirrhosis. Clin Invest Med. 1988;11(1):6-9.
- Villeneuve JP, Rocheleau F, Raymond G. Triamterene kinetics and dynamics in cirrhosis. Clin Pharmacol Ther. 1984;35(6):831-7. doi: 10.1038/clpt.1984.121
- Gentilini P, La Villa G, Marra F, et al. Pharmacokinetics and pharmacodynamics of torasemide and furosemide in patients with diuretic resistant ascites. J Hepatol. 1996;25(4):481-90. doi: 10.1016/s0168-8278(96)80207-8
- Gerbes AL, Remien J, Jüngst D, et al. Evidence for down-regulation of beta-2-adrenoceptors in cirrhotic patients with severe ascites. Lancet. 1986;1(8495):1409-11. doi: 10.1016/s0140-6736(86)91556-4.
- Villeneuve JP, Verbeeck RK, Wilkinson GR, Branch RA. Furosemide kinetics and dynamics in patients with cirrhosis. Clin Pharmacol Ther. 1986;40(1):14-20. doi: 10.1038/clpt.1986.132
- Bakti G, Fisch HU, Karlaganis G, et al. Mechanism of the excessive sedative response of cirrhotics to benzodiazepines: model experiments with triazolam. Hepatology. 1987;7(4):629-38. doi: 10.1002/hep.1840070403
- MacGilchrist AJ, Birnie GG, Cook A, et al. Pharmacokinetics and pharmacodynamics of intravenous midazolam in patients with severe alcoholic cirrhosis. Gut. 1986;27(2):190-5. doi: 10.1136/gut.27.2.190
- Davis M. Cholestasis and endogenous opioids: liver disease and exogenous opioid pharmacokinetics. Clin Pharmacokinet. 2007;46(10):825-50. doi: 10.2165/00003088-200746100-00002
- Ahboucha S, Pomier-Layrargues G, Butterworth RF. Increased brain concentrations of endogenous (non-benzodiazepine) GABA-A receptor ligands in human hepatic encephalopathy. Metab Brain Dis. 2004;19(3-4):241-51. doi: 10.1023/b:mebr.0000043974.89820.22
- Rhee C, Broadbent AM. Palliation and liver failure: palliative medications dosage guidelines. J Palliat Med. 2007;10(3):677-85. doi: 10.1089/jpm.2006.0246
- Zichterman A. Opioid pharmacology and considerations in pain management. May 2007. US Pharmacist (Web). Available at: http://www.uspharmacist.com/continuing_education/ceviewtest/lessonid/105473/. Accessed: 19.09.2021.
- Johnson SJ. Opioid safety in patients with renal or hepatic dysfunction. June 2007. Pain Treatment Topics (Web). Available at: http://pain-topics.org/pdf/Opioids-Renal-Hepatic- Dysfunction.pdf#search="opioids and liver failure". Accessed: 19.09.2021.
- Tegeder I, Lötsch J, Geisslinger G. Pharmacokinetics of opioids in liver disease. Clin Pharmacokinet. 1999;37(1):17-40. doi: 10.2165/00003088-199937010-00002
- Diep U, Chudow M, Sunjic KM. Pharmacokinetic Changes in Liver Failure and Impact on Drug Therapy. AACN Adv Crit Care. 2017;28(2):93-101. doi: 10.4037/aacnacc2017948
- Colson JD. The pharmacology of sedation. Pain Physician. 2005;8(3):297-308.
- Panzer O, Moitra V, Sladen RN. Pharmacology of sedative-analgesic agents: dexmedetomidine, remifentanil, ketamine, volatile anesthetics, and the role of peripheral Mu antagonists. Anesthesiol Clin. 2011;29(4):587-605, vii. doi: 10.1016/j.anclin.2011.09.002
- Olson JC, Wendon JA, Kramer DJ, et al. Intensive care of the patient with cirrhosis. Hepatology. 2011;54(5):1864-72. doi: 10.1002/hep.24622
- Williams RL, Blaschke TF, Meffin PJ, et al. Influence of viral hepatitis on the disposition of two compounds with high hepatic clearance: lidocaine and indocyanine green. Clin Pharmacol Ther. 1976;20(3):290-9. doi: 10.1002/cpt1976203290
- Power BM, Forbes AM, van Heerden PV, Ilett KF. Pharmacokinetics of drugs used in critically ill adults. Clin Pharmacokinet. 1998;34(1):25-56. doi: 10.2165/00003088-199834010-00002
- Bosilkovska M, Walder B, Besson M, et al. Analgesics in patients with hepatic impairment: pharmacology and clinical implications. Drugs. 2012;72(12):1645-69. doi: 10.2165/11635500-000000000-00000
- Andreasen PB, Hutters L. Paracetamol (acetaminophen) clearance in patients with cirrhosis of the liver. Acta Med Scand Suppl. 1979;624:99-105. doi: 10.1111/j.0954-6820.1979.tb00728.x
- Udy AA, Roberts JA, Lipman J. Clinical implications of antibiotic pharmacokinetic principles in the critically ill. Intensive Care Med. 2013;39(12):2070-82. doi: 10.1007/s00134-013-3088-4
- Oyaert M, Spriet I, Allegaert K, et al. Factors impacting unbound vancomycin concentrations in different patient populations. Antimicrob Agents Chemother. 2015;59(11):7073-9. doi: 10.1128/AAC.01185-15
- Mingeot-Leclercq MP, Glupczynski Y, Tulkens PM. Aminoglycosides: activity and resistance. Antimicrob Agents Chemother. 1999;43(4):727-37. doi: 10.1128/AAC.43.4.727
- Kaminsky LS, Zhang ZY. Human P450 metabolism of warfarin. Pharmacol Ther. 1997;73(1):67-74. doi: 10.1016/s0163-7258(96)00140-4
- Graff J, Harder S. Anticoagulant therapy with the oral direct factor Xa inhibitors rivaroxaban, apixaban and edoxaban and the thrombin inhibitor dabigatran etexilate in patients with hepatic impairment. Clin Pharmacokinet. 2013;52(4):243-54. doi: 10.1007/s40262-013-0034-0
- Dasher K, Trotter JF. Intensive care unit management of liver-related coagulation disorders. Crit Care Clin. 2012;28(3):389-98, vi. doi: 10.1016/j.ccc.2012.04.006
- Williamson DR, Boulanger I, Tardif M, et al. Argatroban dosing in intensive care patients with acute renal failure and liver dysfunction. Pharmacotherapy. 2004;24(3):409-14. doi: 10.1592/phco.24.4.409.33168
- Государственный реестр лекарственных средств Минздрава России. Режим доступа: https://grls.rosminzdrav.ru. Ссылка активна на 19.09.2021 [Gosudarstvennyi reestr lekarstvennykh sredstv Minzdrava Rossii. Available at: https://grls.rosminzdrav.ru. Accessed: 19.09.2021 (in Russian)].